This explanatory study investigated the efficacy and safety of azithromycin 1.5% in the target population for which antibiotics are indicated for active trachoma. A targeted treatment study design10,12,13,14,16,28,29,30
(in which the percentage of cure of the initial episode was assessed with a strict control of the confounding factors in affected patients) was considered more relevant than a mass treatment study design31,32,33,34,35,36
(in which clinical and/or microbiological prevalence is assessed in pragmatic conditions in the whole populations). Indeed, the objective was to assess the efficacy of azithromycin eye drops for registration purposes. Therefore, it focussed on individual treatment of patients and it did not assess the prevention of blinding trachoma in a community. The study design was discussed with regulatory authorities before the initiation of the study. For the same reasons, a two‐month follow‐up was agreed to be adequate for the treatment of a disease episode.
The primary endpoint was cure at month 2, defined as a TF0 grade.21
This is a validated and widely‐used tool for the grading of trachoma used in most clinical trials.
Azithromycin 1.5% for 2 or 3 days was demonstrated to be non‐inferior to oral azithromycin. The cure rates in our study were rather high. A review of randomised targeted treatment studies with oral azithromycin shows that clinical cure rates are very variable.10,12,13,14,16,28,29,30,33
Guzey et al
reported a cure rate of 92% at month 3 following repeated doses of azithromycin (10 mg/kg for 3 days).29
Bowman et al
reported a cure rate of 88% at month 6 following a single dose (20 mg/kg).13
In a recent mass treatment study, West et al
reported a cure rate of 91% at month 2 in patients with low chlamydial loads at baseline.36
This high cure rate in our study may be explained by the high compliance to treatment (over 99%) as all instillations were performed by the investigator's staff. In addition, the baseline prevalence in our study was lower than expected17
and than that reported in other studies. 10,12,13,14,16,28,29,30,31,32,33,34,35,36
A low prevalence constitutes a factor for a better outcome and limits reinfection risks soon after episode resolution.
The cure rate 2 months after treatment is unlikely to be affected by the measures against reinfection. Indeed, in a recent Cochrane review, no beneficial effect of face washing alone or in combination with a treatment has been supported after a 6‐month follow‐up.37
It is unclear whether a 12‐month period is long enough to demonstrate its impact.37
Similarly, giving families oral azithromycin is not susceptible to cure the affected children shortly after treatment. Those measures are essential for controlling one of the major confounding factors, that is, reinfection.
The participating countries were very different. In Pakistan, there were more boys and patients were older. It proved difficult to treat patients' contacts in Pakistan. This explains the statistically significant country effect, with lower cure rates in Pakistan than in Guinea.
The incidence of adverse events was low and no adverse events were treatment‐related. However, the children were often too young for directed questioning about adverse events and, probably for cultural reasons, generally did not complain. Many trachoma studies did not report safety data, whilst others reported low incidences of adverse events.12,14,29,30
In conclusion, this clinical trial showed that azithromycin 1.5% twice daily for 2 or 3 days has a similar efficacy to a single oral 20 mg/kg dose of azithromycin for the treatment of episodes of active trachoma in children 2 months after treatment.
Azithromycin 1.5% has several advantages compared to oral azithromycin. In particular, the risk of bacterial resistance should be substantially reduced. Therefore, azithromycin 1.5% may represent an innovative ophthalmic alternative to the WHO's reference treatment. The next step is to assess its effectiveness during pragmatic clinical trials in communities.